Organoboron derivatives and process for coupling organic compounds

ABSTRACT

This invention relates to a process for covalently coupling organic compounds which comprises: reacting an olefinic compound having at least one carbon to carbon double bond or an acetylenic compound having at least one carbon to carbon triple bond with a diboron derivative in the presence of a Group 8-11 metal catalyst to form an organoboron intermediate having an organoboronate residue on at least one carbon atom of the respective double or triple bond; and reacting the organoboron intermediate with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group 8-11 metal catalyst and a suitable base, whereby the olefinic or acetylenic compound is coupled to the organic compound via a direct bond between the carbon atom having the organoboronate residue and the coupling posiitijno. This invention also relates to a process for preparing an organoboron derivative which comprises reacting an olefinic compound having a leaving group in at the allylic position with a diboron derivative in the presence of a Group 8-11 metal catalyst such that the leaving gruop is replaced with an organoboronate residue. The invention further relates to organoborn intermediates and their preparation.

The present invention relates to a process for covalently couplingorganic compounds, in particular to a process for covalently linking anolefinic or acetylenic compound via an organoboron intermediate to otherorganic compounds. The invention also relates to a process for preparingthe organoboron intermediates.

Processes for forming covalent bonds between olefinic or acetyleniccompounds and other organic compounds, both inter- and intra-molecular,are of particular importance to the synthetic organic chemist. Many suchreactions are known, each requiring its own special reaction conditions,solvents, catalysts, activating groups etc. Some known types of couplingreactions involving olefinic moieties include the Michael reaction andreactions described in the following references: Transition Metals inthe Synthesis of Complex Organic Molecules (L. S. Hegedus, UniversityScience Books, 1994, ISBN 0-935702-28-8); Handbook of PalladiumCatalysed Organic Reactions (J. Malleron, J. Fiaud and J. Legros,Academic Press, 1997, ISBN 0-12-466615-9); Palladium Reagents andCatalysts (Innovations in Organic Synthesis by J. Tsuji, John Wiley &Sons, 1995, ISBN 0471-95483-7); and N. Miyuara and A. Suzuki, Chem Rev.1995, 95, 2457-2483.

Catalysts of palladium, its complexes and its salts are well recognisedfor activation of C—H bonds towards coupling reactions. In this regardthe Heck reaction of an alkene or alkyne with an aryl or vinyl halide inthe presence of palladium derivatives has been the subject of intensivestudy. However commercial development of the Heck reaction has notprogressed as rapidly as could have been expected. Other Group 8-11metal catalysts, such as platinum, have also been used to activate suchcarbon bonds.

The success of the Heck reaction depends to a large extent on thesubstrates and the reaction conditions. For example, when twoβ-hydrogens are present in the alkene the reaction generally leads tothe formation of the (E)-alkenes which are often contaminated with thecorresponding (Z)-alkenes.

Although alkene borates (alkenylborates) can be reacted with a varietyof organic molecules to give coupled products via the formation of newcarbon-carbon bonds (See for example the references above) the processfor the preparation of the alkenylborates by the commonly usedhydroboration reaction of alkynes is limited because of the difficultiesthat are encountered through the lack of regiochemistry and/orchemoselectivity (such as the reduction of a number of differentfunctional groups) (See N. Miyuara and A. Suzuki, Chem Rev. 1995, 95,2457-2483).

Improved and/or alternative methodologies are thus required for thesynthesis of organo borates from alkenes and alkynes.

It has now been found that useful organoboron compounds can besynthesised from alkenes and alkynes under mild conditions and in thepresence of a range of substituents. This process overcomes or at leastalleviates one or more of the limitations encountered in the use of thestandard hydroboration methodology. Coupling of the organoboronderivatives with an organic compound may be achieved in the presence ofGroup 8-11 metal catalyst and a suitable base.

Accordingly the present invention provides a process for covalentlycoupling organic compounds which comprises reacting an olefinic organiccompound having at least one carbon to carbon double bond or anacetylenic compound having at least one carbon to carbon triple bondwith a diboron derivative in the presence of a Group 8-11 metal catalystsuch that an organoboronate residue is introduced on one or two of thecarbon atoms of the respective double or triple bond. In this processthe triple bond becomes a double bond, or the double bond becomes asingle bond. Other triple or double bonds may be present and, dependingon the reaction conditions employed, these may or may not also reactwith the diboron derivative.

The diboron derivative may be an ester or other stable derivative ofdiboronic acid. Examples of suitable esters include those of the formula(RO)₂B—B(OR)₂ where R is optionally substituted alkyl or optionallysubstituted aryl or —B(OR)₂ represents a cyclic group of formula

where R′ is optionally substituted alkylene, arylene or other divalentgroup comprising linked aliphatic or aromatic moieties. Preferreddiboron derivatives include4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane[bis(pinacolato)diboronor the pinacol ester of diboronic acid],2,2′-bi-1,3,2-dioxaborolane[bis(ethanediolato)diboron],2,2′-bi-1,3,2-dioxaborinane[bis(n-propanediolato)diboron],5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane[bis(neopentanediolato)diboron],(4R,4′R,5R,5′R)-tetramethyl-2,2′-bi-1,3,2-dioxaborolane,1,1,2,2-tetrakis(2-methoxyethyloxy)diborane,bis((1S,2S,3R,5S)-(+)-pinanediolato)diboron(B—B),(4R,4′R)-diphenyl-2,2′-bi-1,3,2-dioxaborolane,(+/−)-4,4′-bi-[(4-methoxyphenoxy)methyl]-2,2′-bi-1,3,2-dioxaborolane,2,2′-bi-(3aR,7aS)hexahydro-1,3,2-benzodioxaborole, tetraisopropyl(4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′5,5′-tetracarboxylate,(3aR,3′aR,6aS,6′aS)-di-tetrahydro-3aH-cyclopenta[d]-2,2′-bi-1,3,2-dioxaborolane,(3R,6S,3′R,6′S)-di-tetrahydrofuro[3,4-d]-2,2′-bi-1,3,2-dioxaborolane,(+/−)-4,4′-bi-(methoxymethyl)-2,2′-bi-1,3,2-dioxaborolane,2,2′-bi-1,3,2-dioxaborepane,5,5′-dihydroxymethyl-5,5′-dimethyl-2,2′-bi-1,3,2-dioxaborinane,bis(1R,2R,3S,5R-(−)-pinanediolato)diboron(B—B),2,2′-bi-4H-1,3,2-benzodioxaborinine,(+/−)4,4′-bi-(phenoxymethyl)-2,2′-1,3,2-dioxaborolane, (+/−)4,4,4′,4′,6,6′-hexamethyl-2,2′-bi-1,3,2-dioxaborinane,5,5,5′,5′-tetraethyl-2,2′-bi-1,3,2-dioxaborinane,4,4′,5,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborolane,(+/−)-4,4′-dimethyl-2,2′-bi-1,3,2-dioxaborinane,(+/−)-5,5′-dimethyl-2,2′-bi-1,3,2-dioxaborinane, bi-(dinaphtho[2,1-d:1,2-f])-2,2′-bi-1,3,2-dioxaborepine,6,6′-diethyl-2,2′-bi-1,3,6,2-dioxazaborocane,6,6′-dimethyl-2,2′-bi-1,3,6,2-dioxazaborocane,5,5,5′,5′-tetraphenyl-2,2′-bi-1,3,2-dioxaborinane,4,4,4′,4′,7,7,7′,7′-octamethyl-2,2′-bi-1,3,2dioxaborepane,1,1,2,2-tetrakis(neopentyloxy)diborane,(4S,4′S,5S,5′S)-tetramethyl-2,2′-bi-1,3,2-dioxaborolane, tetrabutyl(4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxylate,(4R,4′R,5R,5′R)-N4,N4,N4′,N4′,N5,N5,N5′,N5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxamide,4,4,4′,4′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane. 4,4,4′,4′,6,6,6′,6′-octamethyl-2,2′-bi-1,3,2-dioxaborinane,.3,3′-bi-1,5-dihydro-2,4,3-benzodioxaborepine,(+/−)4,4,4′,4′,5,5′-hexamethyl-2,2′-bi-1,3,2-dioxaborolane,4,4,4′,4′-tetramethyl-2,2′-bi-1,3,2dioxaborolane,5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane,4,4′,5,5′-tetraphenyl-1,3,2-dioxaborolane,4,4′-diphenyl-1,3,2-dioxaborolane and4,4′,6,6′-tetra(tert-butyl)-1,3,2-benxodioxaborole.

Some of the diboron derivatives will be more readily amenable tosubsequent hydrolysis than others and may allow for the use of milderreaction conditions. Furthermore, judicious choice of the diboronderivative used may facilitate control over the reaction productsformed. The diboron ester derivatives may be made following the methodof Brotherton et al. [R. J. Brotherton, A. L. McCloskey, L. L. Petersonand H. Steinberg, J. Amer. Chem. Soc. 82, 6242 (196); R. J. Brotherton,A. L. McCloskey, J. L. Boone and H. M. Manasevit,. J. Amer. Chem. Soc.82, 6245 (1960)]. In this process B(NMe₂)₃, obtained by reaction of BCl₃with NHMe₂, is converted to BrB(NMe₂)₂ by reaction with a stoichiometricamount of BBr₃. Reduction in refluxing toluene with sodium metal givesthe diboron compound [B(NMe₂)₂]₂ which, after purification bydistillation, can be reacted with the alcohol (for example, pinacol) inthe presence of a stoichiometric amount of HCl to give the desired esterproduct. Bis(neopentanediolato)diboron is described by Nguyen et al[Nguyen, P., Lesley, G., Taylor, N. J., Marder, T. B., Pickett, N/L/,Clegg, W., Elsegood, M. R. J., and Norman, N. C., Inorganic Chem. 1994,33, 4623-24]. Other methods for the preparation of the diboronderivatives would be known to those in the art.

The term “organoboronate residue” as used herein refers to the singleboron containing residue formed by cleavage of the boron to boron bondof a diboron derivative. Examples of organoboronate residues are groupsof the formula —B(OR)₂ as defined above.

The terms “organoboron derivative” and “organoboron intermediate” asused herein refer to an organic compound having at least oneorganoboronate residue at a substitution position.

According to another embodiment of the invention there is provided aprocess for covalently coupling organic compounds which comprises:

reacting an olefinic compound having at least one carbon to carbondouble bond or an acetylenic compound having at least one carbon tocarbon triple bond with a diboron derivative in the presence of a Group8-11 metal catalyst to form an organoboron intermediate having anorganoboronate residue on at least one carbon atom of the respectivedouble or triple bond, and

reacting the organoboron intermediate with an organic compound having ahalogen or halogen-like substituent at a coupling position in thepresence of a Group 8-11 metal catalyst and a suitable base, whereby theolefinic or acetylenic compound is coupled to the organic compound via adirect bond between the carbon atom having the organoboronate residueand the coupling position.

It is to be appreciated that the olefinic or acetylenic compound and theorganic compound may be one and the same compound such that the couplingreaction is intramolecular.

It is especially convenient to conduct the process in a single potwithout isolation of the organoboron intermediate, however it has beenfound that the presence of unreacted diboron derivative can interferewith the coupling step, resulting in the formation of unwantedby-products.

Accordingly in another embodiment of the present invention there isprovided a process for covalently coupling organic compounds whichcomprises:

reacting an olefinic compound having at least one carbon to carbondouble bond or an acetylenic compound having at least one carbon tocarbon triple bond with a diboron derivative in the presence of a Group8-11 metal catalyst to form an organoboron intermediate having anorganoboronate residue on at least one carbon atom of the respectivedouble or triple bond,

adding water or water and a suitable base to decompose excess diboronderivative, and

reacting the organoboron intermediate with an organic compound having ahalogen or halogen-like substituent at a coupling position in thepresence of a Group 8-11 metal catalyst and a suitable base, whereby theolefinic or acetylenic compound is coupled to the organic compound via adirect bond between the carbon atom having the organoboronate residueand the coupling position.

Preferably the reaction is conducted in a single pot, although it ispossible to isolate the organoboron intermediate prior to the finalcoupling step. If the reaction is conducted in a single pot it ispreferred that the base added to decompose the diboron derivative issuitable for catalysing the coupling reaction. In this case there is noneed to add stronger base with the organic compound in the couplingreaction.

In another embodiment, after formation of the organoboron intermediate,the coupling of the organoboron intermediate with the organic compoundis achieved by increasing the temperature of the reaction mixture to atemperature sufficient for said coupling reacting to occur. In thisembodiment it may not be necessary to add a stronger base to catalysethe coupling reaction.

In cases where there is a need to remove excess diboron derivative butthe use of water or water and base is deleterious because of thesensitivity of substituents or other factors the excess diboronderivative may be decomposed by addition of mild oxidising agentsfollowing the formation of the organoboron intermediate.

Accordingly in a further embodiment there is provided a process forcovalently coupling organic compounds which comprises:

reacting an olefinic compound having at least one carbon to carbondouble bond or an acetylenic compound having at least one carbon tocarbon triple bond with a diboron derivative in the presence of a Group8-11 metal catalyst to form an organoboron intermediate having anorganoboronate residue on at least one carbon atom of the respectivedouble or triple bond,

adding a mild oxidising agent to decompose excess diboron derivative,and

reacting the organoboron intermediate with an organic compound having ahalogen or halogen-like substituent at a coupling position in thepresence of a Group 8-11 metal catalyst and a suitable base, whereby theolefinic or acetylenic compound is coupled to the organic compound via adirect bond between the carbon atom having the organoboronate residueand the coupling position.

The mild oxidising agent may be any compound which will break the B—Bbond of the diboron derivative but which is not strong enough to breakboron-carbon bonds of the organoboron intermediate. Suitable mildoxidising agents are N-chlorosuccinimide, dioxygen gas, chloramine-T,chloramine-B, 1-chlorotriazole, 1,3-dichloro-5,5-dimethylhydantoin,trichloroisocyanuric acid and dichloroisocyanuric acid potassium salt.

Oxidants such as hydrogen peroxide, ozone, bromine, t-butylhydroperoxide, potassium persulphate, sodium hypochlorite and peracids,are too strong for use in this process; use of strong oxidants does notform part of this invention.

The terms “olefinic” and “olefinic compound” as used herein refer to anyorganic compound having at least one carbon to carbon double bond whichis not part of an aromatic system. The olefinic compounds may beselected from optionally substituted straight chain, branched or cyclicalkenes; and molecules, monomers and macromolecules such as polymers anddendrimers, which include at least one carbon to carbon double bond.Examples of suitable olefinic compounds include but are not limited toethylene, propylene, but-1-ene, but-2-ene, pent-1-ene, pent-2-ene,cyclopentene, 1-methylpent-2-ene, hex-1-ene, hex-2-ene, hex-3-ene,cyclohexene, hept-1-ene, hept-2-ene, hept-3-ene, oct-1-ene, oct-2-ene,cyclooctene, non-1-ene, non-4-ene, dec-1-ene, dec-3-ene, buta-1,3-diene,penta-1,4-diene, cyclopenta-1,4-diene, hex-1,diene, cyclohexa-1,3-diene,cyclohexa-1,4-diene, cyclohepta-1,3,5-triene andcycloocta-1,3,5,7-tetraene, each of which may be optionally substituted.Preferably the straight chain branched or cyclic alkene contains between2 and 20 carbon atoms.

The olefinic compounds may be α,β-unsaturated carbonyl compounds such asα,β-unsaturated esters, aldehydes, ketones, nitriles, or conjugateddienes such as 1,3-cyclopentadiene. The term “conjugated dienes” as usedherein refers to any compound capable of acting as a diene in aDiels-Alder reaction. The olefinic compound may also be an organiccompound having a leaving group in an allylic position or a compoundhaving adjacent double bonds, such as a 1,2-diene.

The term “acetylenic compound” as used herein refers to any compoundhaving at least one carbon to carbon triple bond. The acetyleniccompounds may be selected from optionally substituted straight chain,branched or cyclic alkynes and molecules, monomers and macromoleculessuch as polymers and dendrimers, which include at least one carbon tocarbon triple bond. Examples of suitable acetylene compounds include,but are not limited to acetylene, propyne, but-1-yne, but-2-yne,pent-1-yne, pent-2-yne, hex-1-yne, hex-2-yne, hex-3-yne, cyclohexyne,hep-1-yne, hept-2-yne, hept-3-yne, cycloheptyne, oct-1-yne, oct-2-yne,oct-3-yne, oct-4-yne, cyclooctyne, nonyne, decyne, 1,3,5-trioctyne,2,4-dihexyne, each of which may be optionally substituted. Preferablythe straight chain, branched or cyclic alkyne contains between 1 and 20carbon atoms.

The olefinic or acetylenic compounds may have two or more double ortriple bonds, or may have a combination of double and triple bonds. Byselecting appropriate conditions it is possible to obtain organoboronderivatives in which one or more of these bonds remains intact. Forexample, where the compound has a double bond and a triple bondselection of a suitable catalyst can result in a product in which onlythe triple bond has reacted with the diboron derivative. Selection ofanother set of conditions and/or catalyst may result in preferentialreaction at the double bond. Similarly the molar ratio of diboroncompound to unsaturated compound may be selected to give a particulardesired product. As mentioned above the presence of base can also affectthe outcome of the reaction. It has also been found that heating thereaction mixture after initial reaction can result in somehydrodeboration, thereby altering the product, or proportion ofdifferent products, obtained from the reaction. For example it ispossible to convert some or all of the diboronated product to thecorresponding monoboronated product.

As used herein the term “organic compound having a halogen orhalogen-like substituent at a coupling position” refers to any organiccompound having a carbon to halogen or carbon to halogen-likesubstituent bond at a position where coupling to the organoboroncompound is desired. The organic compound may be aliphatic, olefinic,allylic, acetylenic, aromatic, polymeric or dendritic. The compound maybe an olefinic or acetylenic compound as defined above or part of such acompound. The organic compound may have one or more, preferably between1 and 6, halogen or halogen-like substituents at coupling positions.

The terms “aromatic” and “aromatic compound(s)” as used herein refer toany compound or moiety which includes or consists of one or morearomatic or pseudoaromatic rings. The rings may be carbocyclic orheterocyclic, and may be mono or polycyclic ring systems. Examples ofsuitable rings include but are not limited to benzene, biphenyl,terphenyl, quaterphenyl, naphthalene, tetrahydronaphthalene,1-benzylnaphthalene, anthracene, dihydroanthracene, benzanthracene,dibenzanthracene, phenanthracene, perylene, pyridine, 4-phenylpyridine,3-phenylpyridine, thiophene, benzothiophene, naphthothiophene,thianthrene, furan, pyrene, isobenzofuran, chromene, xanthene,phenoxathiin, pyrrole, imidazole, pyrazole, pyrazine, pyrimidine,pyridazine, indole, indolizine, isoindole, purine, quinoline,isoquinoline, phthalazine, quinoxaline, quinazoline, pteridine,carbazole, carboline, phenanthridine, acridine, phenanthroline,phenazine, isothiazole, isooxazole, phenoxazine and the like, each ofwhich may be optionally substituted. The terms “aromatic” and “aromaticcompound(s)” include molecules, and macromolecules, such as polymers,copolymers and dendrimers which include or consist of one or morearomatic or pseudoaromatic rings. The term “pseudoaromatic” refers to aring system which is not strictly aromatic, but which is stablized bymeans of delocalization of π electrons and behaves in a similar mannerto aromatic rings. Examples of pseudoaromatic rings include but are notlimited to furan, thiophene, pyrrole and the like.

The term “coupling position” as used herein refers to a position on anorganic compound at which coupling to another organic compound isdesired. Each olefinic compound or organic compound may have one ormore, preferably between 1 and 6, coupling positions.

The term “substitution position” as used herein refers to a position onan organic compound at which substitution with an organoboronate residueis desired. Each organic compound may have one or more, preferablybetween 1 and 6, substitution positions. If the organic compound is apolymer or a dendrimer it may have many substitution positions.

In this specification “optionally substituted” means that a group may ormay not be further substituted with one or more groups selected fromalkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl,haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy,haloalkoxy, haloalkenyloxy, haloaryloxy, isocyano, cyano, formyl,carboxyl, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl,nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino,alkynylamino, arylamino, diarylamino, benzylamino, imino, alkylimine,alkenylimine, alkynylimino, arylimino, benzylimino, dibenzylamino, acyl,alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy,alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy,heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl,carboalkoxy, carboaryloxy mercapto, alkylthio, benzylthio, acylthio,sulphonamido, sulfanyl, sulfo and phosphorus-containing groups,alkoxysilyl, silyl, alkylsilyl, alkylalkoxysilyl, phenoxysilyl,alkylphenoxysilyl, alkoxyphenoxy silyl and arylphenoxy silyl. Theoptional substituent should not be significantly deleterious to thereactivity of the compound to which it is attached.

The organic compound with which the organoboron intermediate reacts mustinclude at least one halogen or halogen-like substituent at a couplingposition to enable reaction with the organoboron intermediate. Preferredhalogen substituents include I, Br and Cl. The reactivity of chlorosubstituted aromatic ring compounds can be increased by selection ofappropriate ligands on the Group 8-11 metal catalyst. The terms“halogen-like substituent” and “pseudo-halide” refer to any substituentwhich, if present on an organic compound may undergo substitution withan organoboron intermediate to give a coupled product. Examples ofhalogen-like substituents include triflates and mesylates, diazoniumsalts, phosphates and those described in Palladium Reagents & Catalysts(Innovations in Organic Synthesis by J. Tsuji, John Wiley & Sons, 1995,ISBN 0471-95483-7).

The present invention is based on the finding that in the presence of aGroup 8-11 metal catalyst, diboron derivatives may add across a carbonto carbon double or triple bond of an olefinic or acetylenic compoundsuch that an organoboronate residue is introduced on each of the carbonatoms of the respective double or triple bond, such that the double bondbecomes a single bond and the triple bond becomes a double bond. In thecase of two or more conjugated double bonds the organoboronate residuesmay be introduced on the distal carbon atoms participating in theconjugation resulting in loss of conjugation. In the case of anα,β-unsaturated carbonyl compound, the end-diboronate formed is unstableand the product isolated has a single organoboronate residue on theβ-carbon and the α,β-unsaturation is lost.

The term “distal” as used herein in relation to carbon atomsparticipating in conjugation refers to the carbon atoms at each end ofthe conjugated chain of carbon atoms. For example, the distal carbonatoms in 1,3-butadiene are carbon atoms 1 and 4.

The expression “loss of conjugation” as used herein refers to theconversion of a double bond of a conjugated system into a single bond.This may result in complete loss of conjugation or partial loss ofconjugation. In some cases there may be some rearrangement followingloss of conjugation.

The process according to the present invention is especially suitablefor coupling olefinic or acetylenic compounds containing substituentswhich are reactive with organometallic compounds, such as Grignardreagents or alkyl lithiums, and therefore unsuitable for reacting usingstandard Grignard methodology unless these substituents are firstprotected. One such class of reactive substituents are the activehydrogen containing substituents. The term “active hydrogen containingsubstituent” as used herein refers to a substituent which contains areactive hydrogen atom. Examples of such substituents include but arenot limited to hydroxy, amino, imino, carboxy (including carboxylato),carbamoyl, carboximidyl, sulfo, sulfinyl, sulfinimidyl,sulfinohydroximyl, sulfonimidyl, sulfondiimidyl, sulfonohydroximyl,sultamyl, phosphinyl, phosphinimidyl, phosphonyl, dihydroxyphosphanyl,hydroxyphosphanyl, phosphono (including phosphonato),hydrohydroxyphosphoryl, allophanyl, guanidino, hydantoyl, ureido, andureylene. Of these substituents it is particularly surprising that thereaction can be conducted with hydroxy and primary and secondary aminesubstituents in view of their high reactivity. Carboxyl, sulfo and thelike (i.e. acidic) substituents may require additional base. Otherreactive substituents include trimethylsilyl.

According to this aspect of the invention there is provided a processfor preparing an organoboron derivative comprising reacting a diboronderivative with an olefinic or acetylenic compound having respectivelyat least one carbon to carbon double bond or at least one carbon tocarbon triple bond, and a substituent reactive with organometalliccompounds, in the presence of a Group 8-11 metal catalyst, such that aorganoboronate residue is introduced on one or two of the carbon atomsof the respective double or triple bonds. Preferably the reactivesubstituent is an active hydrogen containing substituent.

Another embodiment of the present invention is based on the finding thatwhen an olefinic compound containing a carbon to carbon double bond anda leaving group at an allylic position, is reacted with a diboronderivative in the presence of a Group 8-11 metal catalyst, the leavinggroup can be replaced by an organoboronate residue. Preferably theleaving group is an ester group.

Accordingly, in this embodiment, there is provided a process forpreparing organoboron derivatives which comprises reacting an olefiniccompound having a leaving group at an allylic substitution position witha diboron derivative in the presence of a Group 8-11 metal catalyst suchthat the leaving group is replaced with an organoboronate residue.

Some of the boron intermediates are novel and represent a further aspectof the present invention. Examples of such novel boron intermediateswhich may be prepared according to the present invention are listedbelow:

2-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-dimethyl-1,3,2-dioxaborinane.

2-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1-ethyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane.

2-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1-phenyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane.

Methyl(Z)-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-nonenoate.

(E)4-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one.

(Z)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one.

2-[(E)-1-(1-Cyclohexen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

1-[(E)-1,2-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]cyclohexanol.

(E)-N,N-Dimethyl-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amine.

(E)-3-Ethyl-1,2-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-amine.

(E)-N,N-Di(2-propynyl)-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amine.

4,4,5,5-Tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)bicyclo[2.2.1]hept-2-yl]-1,3,2-dioxaborolane.

4,4-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexanone.

4,4-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexanone.

4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-butanone.

4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-butanone.

4,4,5,5-Tetramethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclohexen-1-yl]-1,3,2-dioxaborolane.

(Z)-1,5-Diphenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-one.

3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal.

4,4,5,5-Tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,6-cyclooctatrien-1-yl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,7-cyclooctatrien-1-yl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-cycloocten-1-yl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-3-en-8-yl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-8-en-4-yl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-(4-methylcyclohexyl)-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-(3-methylcyclohexyl)-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-7-ynyl]-1,3,2-dioxaborolane.

4,4,5,5-Tetramethyl-2-[(1E,7E)-2,7,8-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-octadienyl]-1,3,2-dioxaborolane.

2-[(Z)-1-Butyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-3-ynyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

2-[(1Z,3Z)-1-Butyl-2,3,4-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-octadienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

2-[(Z)-2-(4H-1,3,2-Benzodioxaborinin-2-yl)-1,2-diphenylethenyl]-4H-1,3,2-benzodioxaborinine.

2-[(Z)-1,2-Diphenyl-2-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)ethenyl]-4,4,6-trimethyl-1,3,2-dioxaborinane.

2-[(Z)-2-(5,5-Diethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-diethyl-1,3,2-dioxaborinane.

(2-{(Z)-2-[4-(Phenoxymethyl)-1,3,2-dioxaborolan-2-yl]-1,2-diphenylethenyl}-1,3,2-dioxaborolan-4-yl)methylphenyl ether.

(1S,2S,6R,8S)-4-{(Z)-1,2-diphenyl-2-[(1R,2R,6S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]dec-4-yl]ethenyl}-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decane.

(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)Tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborole.

(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)Tetrahydrofuro[3,4-d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydrofuro[3,4-d][1,3,2]dioxaborole.

2-[(Z)-1,2-Diphenyl-2-(4-phenyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4-phenyl-1,3,2-dioxaborolane.

(3aR,7aS)-2-{(Z)-2-[(3aR,7aS)Hexahydro-1,3,2-benzodioxaborol-2-yl]-1,2-diphenylethenyl}hexahydro-1,3,2-benzodioxaborole.

In yet another aspect, there is provided a process for preparing anorganic boronic acid derivative which comprises reacting an olefiniccompound having a leaving group at an allylic substitution position anda substituent reactive with organometallic compounds with a diboronderivative in the presence of a Group 8-11 metal catalyst, such that theleaving group is substituted with an organoboronate residue.

As used herein, the term “leaving group” refers to a chemical groupwhich is capable of being displaced by an organoboronate residue.Suitable leaving groups are apparent to those skilled in the art andinclude halogen and halogen-like substituents, as well as ester groups.

The term “allylic substitution position” as used herein refers to aposition on the olefinic compound at which substitution with anorganoboronate residue is desired and which is located on a carbon atomwhich is directly next to a carbon atom which is part of an olefiniccarbon to carbon double bond.

In the above definitions, the term “alkyl”, used either alone or incompound words such as “alkenyloxyalkyl”, “alkylthio”, “alkylamino” and“dialkylamino” denotes straight chain, branched or cyclic alkyl,preferably C₁₋₂₀ alkyl or cycloalkyl. Examples of straight chain andbranched alkyl include methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec-butyl, tert-butyl, amyl, isoamyl, sec-amyl,1,2-dirnethylpropyl, 1,1-dimethyl-propyl, hexyl, 4-ethylpentyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl,2,2-imethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl,1,3-dimethylbutyl, 1,2,2,-trimethylpropyl, 1,1,2-trimethylpropyl,heptyl, 5-methoxyhexyl, 1-methylhexyl, 2,2-dimethylpentyl,3,3-dimethylpentyl, 4,4-dimethylpentyl, 1,2-dimethylpentyl,1,3-dimethylpentyl, 1,4-dimethyl-pentyl, 1,2,3,-trimethylbutyl,1,1,2-trimethylbutyl, 1,1,3-trimethylbutyl, octyl, 6-methylheptyl,1-methylheptyl, 1,1,3,3-tetramethylbutyl, nonyl, 1-, 2-, 3-, 4-, 5-, 6-or 7-methyl-octyl, 1-, 2-, 3-, 4- or 5-ethylheptyl, 1-, 2- or3-propylhexyl, decyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-methylnonyl, 1-,2-, 3-, 4-, 5- or 6-ethyloctyl, 1-, 2-, 3- or 4-propylheptyl, undecyl,1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-methyldecyl, 1-, 2-, 3-, 4-, 5-, 6-or 7-ethylnonyl, 1-, 2-, 3-, 4- or 5-propylocytl, 1-, 2- or3-butylheptyl, 1-pentylhexyl, dodecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-,9- or 10-methylundecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-ethyldecyl, 1-,2-, 3-, 4-, 5- or 6-propylnonyl, 1-, 2-, 3- or 4-butyloctyl,1-2-pentylheptyl and the like. Examples of cyclic alkyl include mono- orpolycyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and thelike.

The term “alkoxy” denotes straight chain or branched alkoxy, preferablyC₁₋₂₀ alkoxy. Examples of alkoxy include methoxy, ethoxy, n-propoxy,isopropoxy and the different butoxy isomers.

The term “alkenyl” denotes groups formed from straight chain, branchedor cyclic alkenes including ethylenically mono-, di- or poly-unsaturatedalkyl or cycloalkyl groups as previously defined, preferably C₂₋₂₀alkenyl. Examples of alkenyl include vinyl, allyl, 1-methylvinyl,butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl,1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl,3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl,1-decenyl, 3-decenyl, 1,3-butadienyl, 1-4,pentadienyl,1,3-cyclopentadienyl, 1,3-hexadienyl, 1,4-hexadienyl,1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl,1,3,5-cycloheptatrienyl and 1,3,5,7-cyclooctatetraenyl.

The term “alkynyl” denotes groups formed from straight chain, branchedor cyclic alkyne including those structurally similar to the alkyl andcycloalkyl groups as previously defined, preferably C₂₋₂₀ alkynyl.Examples of alkynyl include ethynyl, 2-propynyl and 2- or 3-butynyl.

The term “acyl” either alone or in compound words such as “acyloxy”,“acylthio”, “acylamino” or “diacylamino” denotes carbamoyl, aliphaticacyl group and acyl group containing an aromatic ring, which is referredto as aromatic acyl or a heterocyclic ring which is referred to asheterocyclic acyl, preferably C₁₋₂₀ acyl. Examples of acyl includecarbamoyl; straight chain or branched alkanoyl such as formyl, acetyl,propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl,2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl,decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl,pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyland icosanoyl; alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl,t-butoxycarbonyl, t-pentyloxycarbonyl and heptyloxycarbonyl;cycloalkylcarbonyl such as cyclopropylcarbonyl, cyclobutylcarbonyl,cyclopentylcarbonyl and cyclohexylcarbonyl; alkylsulfonyl such asmethylsulfonyl and ethylsulfonyl; alkoxysulfonyl such as methoxysulfonyland ethoxysulfonyl; aroyl such as benzoyl, toluoyl and naphthoyl;aralkanoyl such as phenylalkanoyl (e.g. phenylacetyl, phenylpropanoyl,phenylbutanoyl, phenylisobutylyl, phenylpentanoyl and phenylhexanoyl)and naphthylalkanoyl (e.g. naphthylacetyl, naphthylpropanoyl andnaphthylbutanoyl; aralkenoyl such as phenylalkenoyl (e.g.phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentenoyl andphenylhexenoyl and naphthylalkenoyl (e.g. naphthylpropenoyl,naphthylbutenoyl and naphthylpentenoyl); aralkoxycarbonyl such asphenylalkoxycarbonyl (e.g. benzyloxycarbonyl); aryloxycarbonyl such asphenoxycarbonyl and napthyloxycarbonyl; aryloxyalkanoyl such asphenoxyacetyl and phenoxypropionyl; arylcarbamoyl such asphenylcarbamoyl; arylthiocarbamoyl such as phenylthiocarbamoyl;arylglyoxyloyl such as phenylglyoxyloyl and naphthylglyoxyloyl;arylsulfonyl such as phenylsulfonyl and napthylsulfonyl;heterocycliccarbonyl; heterocyclicalkanoyl such as thienylacetyl,thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl,thiazolylacetyl, thiadiazolylacetyl and tetrazolylacetyl;heterocyclicalkenoyl such as heterocyclicpropenoyl,heterocyclicbutenoyl, heterocyclicpentenoyl and heterocyclichexenoyl;and heterocyclicglyoxyloyl such as thiazolylglyoxyloyl andthienylglyoxyloyl.

The terms “heterocyclic”, “heterocyclyl” and “heterocycl” as used hereinon their own or as part of a term such as “heterocyclicalkenoyl”,“heterocycloxy”or “haloheterocyclyl” refer to aromatic, pseudo-aromaticand non-aromatic rings or ring systems which contain one or moreheteroatoms selected from N, S, O and P and which may be optionallysubstituted. Preferably the rings or ring systems have 3 to 20 carbonatoms. The rings or ring systems may be selected from those describedabove in relation to the definition of “aromatic compound(s)”.

The term “aryl” as used herein on its own or as part of a group such as“haloaryl” and “aryloxycarbonyl” refers to aromatic and pseudo-aromaticrings or ring systems composed of carbon atoms, optionally together withone or more heteroatoms. Preferably the rings or ring systems havebetween 3 and 20 carbon atoms. The rings or ring systems may beoptionally substituted and may be selected from those described above inrelation to the definition of “aromatic compound(s)”.

The term “Group 8-11 metal catalyst” as used herein refers to a catalystcomprising a metal of Groups 8-11 of the periodic table described inChemical and Engineering News, 63(5), 27, 1985. Examples of such metalsinclude Ni, Pt and Pd. Preferably the catalyst is a platinum catalyst,although analogous catalysts of other Group 8-11 metals may also beused. The Group 8-11 metal catalyst may be a platinum complex. Examplesof suitable platinum catalysts include but are not limited to Pt(dba)₂,Pt(PPh₃)₂Cl₂, PtCl₂, Pt(OAc)₂, PtCl₂(dppf)CH₂Cl₂, Pt(PPh₃)₄ and relatedcatalysts which are complexes of phosphine ligands, (such as(Ph₂P(CH₂)_(n)PPh₂) where n is 2 to 4, P(o-tolyl)₃, P(i-Pr)₃,P(cyclohexyl)₃, P(o-MeOPh)₃, P(p-MeOPh)₃, dppp, dppb, TDMPP, TTMPP,TMPP, TMSPP and related water soluble phosphines), related ligands (suchas triarylarsine, triarylantimony, triarylbismuth), phosphite ligands(such as P(OEt)₃, P(O-p-tolyl)₃, P(O-o-tolyl)₃ and P(O-iPr)₃) and othersuitable ligands including those containing P and/or N atoms forco-ordinating to the platinum atoms, (such as for example pyridine,alkyl and aryl substituted pyridines, 2,2′-bipyridyl, alkyl substituted2,2′-bipyridyl and bulky secondary or tertiary amines), and other simpleplatinum salts either in the presence or absence of ligands. Theplatinum catalysts include platinum and platinum complexes supported ortethered on solid supports, such as platinum on carbon, as well asplatinum black, platinum clusters and platinum clusters containing othermetals.

Examples of suitable palladium catalysts include but are not limited toPd₃(dba)₃, PdCl₂, Pd(OAc)₂, PdCl₂(dppf)CH₂Cl₂, Pd(PPh₃)₄ and relatedcatalysts which are complexes of phosphine ligands, (such as(Ph₂P(CH₂)_(n)PPh₂) where n is 2 to 4, P(o-tolyl)₃, P(i-Pr)₃,P(cyclohexyl)₃, P(o-MeOPh)₃, P(p-MeOPh)₃, dppp, dppb, TDMPP, TTMPP,TMPP, TMSPP and related water soluble phosphines), related ligands (suchas triarylarsine, triarylantimony, triarylbismuth), phosphite ligands(such as P(OEt)₃, P(O-p-tolyl)₃, P(O-o-tolyl)₃ and P(O-iPr)₃) and othersuitable ligands including those containing P and/or N atoms forco-ordinating to the palladium atoms, (such as for example pyridine,alkyl and aryl substituted pyridines, 2,2′-bipyridyl, alkyl substituted2,2′-bipyridyl and bulky secondary or tertiary amines), and other simplepalladium salts either in the presence or absence of ligands. Thepalladium catalysts include palladium and palladium complexes supportedor tethered on solid supports, such as palladium on carbon, as well aspalladium black, palladium clusters and palladium clusters containingother metals and palladium in porous glass as described in J. Li, A.W-H. Mau and C. R. Strauss, Chemical

Communications, 1997, p1275. The same or different Group 8-11 metalcatalysts may be used to catalyse different steps in the process. TheGroup 8-11 metal catalyst may also be selected from those described inU.S. Pat. No. 5,686,608. In certain reactions there are advantages inusing ligands with altered basicity and/or steric bulk. Examples ofsuitable Ni catalysts include nickel black, Raney nickel, nickel oncarbon and nickel clusters or a nickel complex. Examples of othersuitable Group 8-11 metal catalysts include those of Au, Rh, Ru, Fe, Co,Zn, Hg, Ag, Os, Ir and analogous complexes of these metals etc.Preferred catalysts are those that readily undergo oxidative additionand reductive elimination. One skilled in the art would be able toselect a suitable catalyst on this basis. Catalysts of platinum arepreferred. The Group 8-11 metal catalyst may additional contain othermetals.

The process may be performed in any suitable solvent or solvent mixture.Examples of such solvents include lower alcohols, and their esters withthe lower aliphatic carboxylic acids, lower aliphatic ketones, cyclicand the lower secondary and tertiary amines, amides of the loweraliphatic carboxylic acids and lower aliphatic secondary amines, DMSO,aromatic or aliphatic hydrocarbons, nitromethane, acetonitrile,benzonitrile, ethers, polyethers, cyclic ethers, lower aromatic ethers,and mixtures thereof, including mixtures with other solvents.

Preferred solvents include protic solvents such as methanol, ethanol,isopropanol and n-butanol, and non-protic solvents such as n-heptane,acetonitrile, acetone, DMSO, DMF, dioxane, DME, diethyl ether, THF,toluene or mixtures thereof with other solvents. Exclusion of water fromthe solvents is generally not essential and in some cases the presenceof water is preferred. The addition of further diboron derivative may beuseful when the solvents are not anhydrous.

It has been generally accepted that reactions of diboron derivativesshould be conducted in the absence of air. However it has beensurprisingly found that some reactions of diboron derivatives witholefinic or acetylenic compounds can be conducted in the presence ofair. The presence of air/oxygen has been found to promote or increasethe rate of the reaction, giving more product in a shorter time period.Other promoters may also be used to provide this effect. This is animportant finding as the requirement for an inert atmosphere can presentdifficulties for commercial scale up and substantially increase themanufacturing costs. The present findings that reactions between diboronderivatives and olefinic or acetylenic compounds can precede efficientlyin the presence of both air and moisture substantially increases thecommercial potential of these reactions.

The temperature at which each step of the process according to theinvention is conducted will depend on a number of factors including thedesired rate of reaction, solubility and reactivity of the reactants inthe selected solvent, boiling point of the solvent, etc. The temperatureof the reaction will generally be in the range of −100 to 250° C. In apreferred embodiment the process is performed at a temperature between 0and 120° C., more preferably between 0 and 80° C., and most preferablybetween 40 and 80° C.

The term “suitable base” as used herein refers to a basic compoundwhich, when present in the reaction mixture, is capable of catalysing,promoting or assisting reaction between reactants. In particular asuitable base is required to catalyse the reaction between theorganoboron derivative and the organic compound. A suitable base mayalso be added to the reaction medium to alter the products of thereaction of the diboron derivative with the olefinic or acetyleniccompound. For example, the addition of base may result in a product withone organoboronate residue at one carbon atom of the relevant bond,rather than at both. Examples of bases which are suitable for catalysingthe reaction of the organoboron derivative and the organic compoundinclude aryl and alkyl carboxylates (for example potassium acetate),fluorides, hydroxides and carbonates of Li, Na, K, Rb, Cs, ammonium,alkylamnmonium, Mg, Ca, & Ba; phosphates and arylphosphates of Li, Na,K, Rb and Cs; phosphate esters (eg. C₆H₅OP(O)(ONa)₂) of Li, Na, K, Rb,Cs, ammonium and alkylammonium; phenoxides of Li, Na, K, Rb and Cs;alkoxides of Li, Na, K, Rb and Cs; and thallium hydroxide. Some of thesebases may be used in conjunction with a phase transfer reagent, such asfor example tetraalkylammonium salts or the crown ethers. The weaker ofthese bases may require some heating to allow the coupling reaction toproceed. Examples of bases suitable for decomposing excess diboronderivative and/or catalysing reaction of the organoboron intermediatewith the organic compound generally without much heating include thestronger bases listed above, including cesium carbonate, potassiumcarbonate, potassium phosphate and alkali metal hydroxides.

In a further aspect of the invention there is provided a process forpreparing an organoboron intermediate, comprising reacting a diboronderivative with an olefinic compound having at least one carbon tocarbon double bond or an acetylenic compound having at least one carbonto carbon triple bond in the presence of a Group 8-11 metal catalystsuch that an organoboronate residue is introduced on one or two of thecarbon atoms of the respective double or triple bond.

A first step in the purification of the intermediate so formed may bethe decomposition of any excess diboron derivative by the use of water,water and suitable base, or by the use of a mild oxidising agent.

In a further aspect of the invention, there is provided a process forthe preparation of an organo boronic acid by hydrolysing the organoboronintermediate as hereinbefore described using established procedures. Theease of hydrolysis is a function of the diboronic ester used. Somealkene borate intermediates are more amenable to hydrolysis than thosederived from bis(pinacolato)diboron.

The present invention provides a novel route to some chiral compounds.In this regard the conversion of a double bond having a substituent onone or both ends, or being part of a cyclic structure, to a single bondproduces new chiral centres. The stereoselective nature of the reactionunder certain conditions of the olefinic compound with the diboronderivative can result in products with a high enantiomeric excess,especially if a chiral diboron derivative is used having an enantiomericexcess of at least one enantiomer over another. Similarly it is possibleto react the diboron derivatives with acetylenic compounds to produceparticular geometric isomers, which may also be chiral if chiral diboronderivatives are used. Chiral intermediates and end products (having anenantiomeric excess of at least one enantiomer over another) may beproduced by the use of chiral borate esters. For example the chiralityof an organoboron intermediate can be transferred to a coupled product.

According to another aspect, the present invention provides a processfor covalently coupling organic compounds which comprises reacting anorganoboron derivative prepared as hereinbefore described with anorganic compound having a halogen or halogen-like substituent at acoupling position in the presence of a Group 8-11 metal catalyst and asuitable base.

In a further aspect there is provided a “one-pot” procedure forcovalently coupling organic compounds comprising reacting:

(i) an olefinic organic compound; or

(ii) an acetylenic compound

with a diboron derivative as hereinbefore defined to form an organoboronintermediate and reacting the organoboron derivative in situ with anorganic compound having a halogen or halogen-like substituent at acoupling position in the presence of a Group 8-11 metal catalyst and asuitable base to form a direct bond between the coupling position and acarbon atom of the organoboron derivative to which the organoboronateresidue is attached.

The process according to the present invention is applicable tochemistry on solid polymer support or resin bead in the same manner asconventional chemistry is used in combinatorial chemistry and in thepreparation of chemical libraries. Thus a suitable organic compoundhaving a halogen or halogen-like substituent at a coupling positionwhich is chemically linked via a linking group to a polymer surface maybe reacted with an organoboron derivative in the presence of a Group8-11 metal catalyst and a suitable base to form a coupled product linkedto the surface of the polymer. Excess reagents and by-products may thenbe washed away from the surface leaving only the reaction product on thesurface. The coupled product may then be isolated by appropriatecleavage of the chemical link from the polymer surface. The process isalso possible using the alternative strategy of reacting: (i) anolefinic organic compound, or (ii) an acetylenic compound, linked to apolymer surface with a diboron derivative as previously described toform an organoboron derivative chemically linked to the polymer surface.This derivative may then be reacted with an organic compound having ahalogen or halogen-like substituent at a coupling position in thepresence of a Group 8-11 metal catalyst and a suitable base to preparethe coupled product chemically linked to the polymer. Excess reactantsand by-products may be removed by suitable washing and the coupledproduct may be isolated by chemically cleaving the link to the polymer.

The term “linking group” as used herein refers to any chain of atomslinking one organic group to another. Examples of linking groups includepolymer chains, optionally substituted alkylene group and any othersuitable divalent group.

It is also possible to prepare polymers by reaction of organoboronderivatives having more than one organoboronate residue with organiccompounds having more than one halogen or halogen-like substituent. Ifthe organic compound has three or more halogen or halogen-likesubstituents which react with the organoboron derivative and/or theorganoboron derivative has three or more organoboronate residues then itis possible to prepare dendritic molecules in accordance with theprocess of the present invention.

The organic compounds which are to be coupled may be separate moleculesor may be linked together such that the organoboron derivative formedafter reaction with the diboron derivative is able to react at acoupling position located elsewhere in the molecule so as to provide foran intramolecular reaction, such as a ring closure reaction.

The process according to the invention is also useful for thepreparation of reactive intermediates which are capable of taking partin further reactions or rearrangements. These reactive intermediates maybe the organoboron derivatives or the coupled products. For example,some derivatives may take part in one or more of the palladium catalysedreactions of organoboron compounds described by Miyaura and Suzuki inChem. Rev. 1995, 95 2457-2483.

The process according to the present invention allows the linking oforganic compounds in mild conditions and avoids the use of expensive,difficult to remove and/or toxic reagents and solvents. In this regardboron and boron compounds are generally non-toxic. It also allows thereaction to be performed in the presence of air and moisture. Thereactions may also be performed in relatively cheap solvents such asmethanol and ethanol and, in view of the improved control over thereaction steps, it is envisaged that it would be possible to perform thereactions on an industrial scale. The process also allows the linking oforganic compounds which contain active hydrogen substituents without theneed to protect those substituents during the reaction.

The following Examples are provided to illustrate some preferredembodiments of the invention. However, it is to be understood that thefollowing description is not to supersede the generality of theinvention previously described.

EXAMPLES Example 12-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.178 g; 1.0 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the open tube was heated at 80° C. withstirring for 10 hours. GC analysis showed a peak corresponding to thediboronic ester of diphenylacetylene at 17.0 minutes as the principalproduct (94%), together with a trace of the monoboronic ester (<0.5%).

An identical reaction carried out under an atmosphere of nitrogen gave,after 10 hours, unreacted starting material, together with a peakcorresponding to 50% conversion of starting material to the diboronicester of diphenylacetylene at 17.0 minutes as the principal product.

Example 22-[(Z)-1,2-Diphenylethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxabbrolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles),tetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) andpotassium acetate (0.196 g; 2.0 mmoles) were placed in a Schlenk tubeunder an atmosphere of nitrogen. DMF (5 mL, dried over 4 Å molecularsieve) was added under argon, and the tube was heated at 80° C. withstirring for 5 hours. GC analysis showed product peaks corresponding tocis-stilbene at 7.9 minutes (4%), the monoboronic ester ofdiphenylacetylene at 14.0 minutes (47%) and the diboronic ester ofdiphenylacetylene at 17.0 minutes (44%). Heating for a further 69 hoursat 80° C. gave cis-stilbene (15%) and the monoboronic ester (88%), atthe expense of the diboronic ester (<2%).

Example 32-[(Z)-1,2-Diphenylethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles),tetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 20 hours. GC analysis confirmed effectivelyquantitative formation of the diboronic ester (>98%). Potassium acetate(0.196 g; 2.0 mmoles) was added, and heating was continued for a further69 hours at 80° C. Approximately 75% of the diboronic ester underwenthydrodeboration to give the monoboronic ester.

Example 42-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles) andtetrakis(triphenylphosphine)palladium (0.035 g; 0.030 mmoles) wereplaced in a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL,dried over 4 Å molecular sieve) was added under argon, and the tube washeated at 80° C. with stirring for 20 hours. GC analysis showed a peakcorresponding to the diboronic ester of diphenylacetylene at 17.0minutes as the principal product (>97%).

Example 52-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles) andcis-bis(triphenylphosphine)dichloroplatinum(II) (0.024 g, 0.030 mmoles)were placed in a Schlenk tube under an atmosphere of nitrogen. DMF (5mL, dried over 4 Å molecular sieve) was added under argon, and the tubewas heated at 80° C. with stirring for 91 hours. GC analysis showed apeak corresponding to the diboronic ester of diphenylacetylene at 17.0minutes (23%).

Example 62-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. THF (5 mL) was addedunder argon, and the tube was heated at 80° C. with stirring for 5hours. GC analysis showed a peak corresponding to the diboronic ester ofdiphenylacetylene at 17.0 minutes as the principal product (>95%).

Example 72-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using dioxane (5 mL)as the solvent in place of THF. The diboronic ester of diphenylacetylenewas the principal product (>95%).

Example 82-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out usingdichloromethane (5 mL) as the solvent in place of THF. The reaction wasallowed to proceed at 80° C. for 22 hours. The diboronic ester ofdiphenylacetylene was the principal product (>95%).

Example 92-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using toluene (5 mL,dried over 4 Å molecular sieve) as the solvent in place of THF. Thediboronic ester of diphenylacetylene was the principal product (>95%).

Example 102-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using acetonitrile(5 mL, dried over 4 Å molecular sieve) as the solvent in place of THF.After 1.5 hours reaction time, the diboronic ester of diphenylacetylenewas the principal product (>95%).

Example 112-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using n-heptane (5mL, dried over 4 Å molecular sieve) as the solvent in place of THF. Thecatalyst appeared to be largely insoluble in this medium. The reactionwas allowed to proceed at 80° C. for 20 hours. The diboronic ester ofdiphenylacetylene was the principal product (>92%).

Example 122-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using acetone (5 mL)as the solvent in place of THF. The reaction was allowed to proceed at80° C. for 20 hours. The diboronic ester of diphenylacetylene was theprincipal product (>95%).

Example 132-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The reaction described in Example 6 was carried out using n-butanol (5mL) as the solvent in place of THF. After 1.5 hours at 80° C., gcanalysis showed the diboronic ester of diphenylacetylene as theprincipal product (88%), together with the monoboronic ester (5%).Heating for an additional 18 hours at 80° C. gave the diboronic ester ofdiphenylacetylene (66%), the monoboronic ester (19%) and cis-stilbene(4%).

Example 144,4,5,5-Tetramethyl-2-[(Z)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butenyl]-1,3,2-dioxaborolane2-[(1Z,3Z)-2,3-Diethyl-1,4-diphenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-butadienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-[(1Z,3Z)-1-Ethyl-2,3-diphenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 1-phenylbutyne(0.143 g; 1.1 mmoles) and bis(dibenzylideneacetone)platinum Pt(dba)₂(0.020 g; 0.030 mmoles) were placed in a Schlenk tube under anatmosphere of nitrogen. Toluene (5 mL, dried over 4 Å molecular sieve)was added under argon, and the tube was heated at 70° C. with stirringfor 63 hours. GC analysis showed the peak corresponding to the diboronicester of 1-phenylbutyne at 14.2 minutes (53%), and a peak at 13.8minutes (8S), which is shown by mass spectrometry to be an isomeric formof the diboronic ester of 1-phenylbutyne. There was also a peak at 17.8minutes (25%), corresponding to the coupling of two monoboronate esters.

Example 154,4,5,5-Tetramethyl-2-[(Z)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butenyl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1-phenyl-1-butyne (0.143 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the open tube was heated at 80° C. withstirring for 2 hours. GC analysis showed a peak corresponding to thediboronic ester of 1-phenyl-1-butyne at 14.2 minutes as the principalproduct (>95%).

An identical reaction mixture that was run under an atmosphere ofnitrogen gave, after 2 hours, unreacted starting material, together witha peak corresponding to 50% conversion of starting material to thediboronic ester of 1-phenyl-1-butyne at 14.2 minutes as the principalproduct:

Example 162-[(Z)-1-Ethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butenyl]-4,4,5,5-tetramethyl-1,2-oxaborolan-3-ol2-[(Z)-1-Ethyl-1-butenyl]-4,4,5,5-tetramethyl-1,2-oxaborolan-3-ol

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 3-hexyne(0.094 g; 1.1 mmoles) and tetrakis(triphenylphosphine)platinum (0.037 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 80° C. with stirring for 3.3 hours. GCanalysis showed the presence of the product diboronic ester at 10.9minutes as the principal product (>98%). Potassium carbonate (0.200 g,2.0 mmoles) was added under argon. The tube was heated for a further 66hours at 80° C., and gc analysis showed the presence of unchangeddiboronic ester at (30%) and the monoboronic ester at 3.7 minutes (66%)arising from monohydrodeboration of the diboronic ester.

Example 172-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-dimethyl-1,3,2-dioxaborinane

The neopentyl ester of diboronic acid (0.226 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at100° C. with stirring for 72 hours. GC analysis showed peakscorresponding to the diboronic ester of diphenylacetylene at 18.2minutes (91%), and the monoboronic ester at 15.0 minutes (7%) as theprincipal products.

Example 182-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1-ethyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane

The neopentyl ester of diboronic acid (0.226 g; 1.0 mmole), 3-hexyne(0.094 g; 1.1 mmoles) and tetrakis(triphenylphosphine)platinum (0.037 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 100° C. with stirring for 4 hours. GCanalysis showed a peak corresponding to the diboronic ester of 3-hexyneat 12.2 minutes (86%).

Example 192-[(Z)-2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-1-phenyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane

The neopentyl ester of diboronic acid (0.226 g; 1.0 mmole), 1-phenylbutyne (0.143 g; 1.1 mmoles) and tetrakis(triphenylphosphine)platinum(0.037 g; 0.030 mmoles) were placed in a Schlenk tube under anatmosphere of nitrogen. DMF (5 mL, dried over 4 Å molecular sieve) wasadded under argon, and the tube was heated at 70° C. with stirring for86 hours. GC analysis showed a peak corresponding to the diboronic esterof 1-phenyl butyne at 15.7 minutes (81%).

Example 20 Methyl(Z)-2,3-bis(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-nonenoate

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),methyl-2-nonynoate (0.185 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 18 hours. GC analysis showed the presence ofthe product diboronic ester at 15.6 minutes as the principal product(98%). Potassium acetate (0.160 g, 1.6 mmoles) was added under argon.The tube was heated for a further 18 hours at 80° C., and gc analysisshowed the presence of one principal product at 11.0 minutes (>90%)corresponding to a monoboronic ester arising from hydrodeboration.

Example 21(E)-4-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one(Z)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),4-phenyl-3-butyne-2-one (0.150 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 42 hours. GC analysis showed the productmonoboronic esters at 11.5 minutes (11%) and 11.9 minutes (23%).

Example 222-[(E)-1-(1-Cyclohexen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1-ethynylcyclohexene (0.126 g; 1.2 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 50 hours. GC analysis showed a peakcorresponding to the product diboronic ester at 15.2 minutes (78%).

Example 231-[(E)-1,2-bis(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]cyclohexanol

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1-ethynyl-cyclohexan-1-ol (0.140 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 120 hours. GC analysis showed a peakcorresponding to the product diboronic ester at 15.6 minutes (94%).

Example 24(E)-N,N-Dimethyl-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amineOrN-[(E)-2,3-bis(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propenyl]-N,N-dimethylamine

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1-dimethylamino-2-propyne (0.095 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 48 hours. GC analysis showed a peakcorresponding to the product diboronic ester at 10.8 minutes (85%).

Example 25(E)-3-Ethyl-1,2-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-amineOr(E)-1,1-Diethyl-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propenylamine

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),3-amino-3-ethyl-1-pentyne (0.135 g; 1.2 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 48 hours. GC analysis showed a peakcorresponding to the product diboronic ester at 13.1 minutes (38%), anda monoboronic ester at 7.6 minutes (60%).

Example 26(E)-N,N-Di(2-Propynyl)-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amineOrN-[(E)-2,3-bis(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propenyl]-N,N-di(2-propynyl)amine

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),tripropargylamine (0.144 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 424 hours. GC analysis showed a peakcorresponding to the product diboronic ester at 13.8 minutes (63%).

Example 274,4,5,5-Tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)bicyclo[2.2.1]hept-2-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), norbornylene(0.188 g; 2.0 mmoles) and tetrakis(triphenylphosphine)platinum (0.037 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 80° C. with stirring for 92 hours, andthen at 100° C. for 73 hours. GC analysis showed a peak corresponding tothe diboronic ester at 12.9 minutes (>95%).

Example 284,4,5,5-Tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)bicyclo[2.2.1]hept-2-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), norbornylene(0.188 g; 2.0 mmoles) and tris(dibenzylideneactone)dipalladium (0.027 g,0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 80° C. with stirring for 92 hours. GCanalysis showed a peak corresponding to the diboronic ester at 12.9minutes (8%).

Example 294,4-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexanone

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),4,4-dimethyl-2-cyclohexen-1-one (0.137 g; 1.1 mmoles) andbis(benzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed in aSchlenk tube under an atmosphere of nitrogen. Toluene (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at70° C. with stirring for 17 hours. GC analysis showed a peakcorresponding to 15% conversion to the boronic ester of4,4-dimethyl-2-cyclohexen-1-one at 9.8 minutes.

Example 304-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-butanone

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),trans-4-phenyl-3-buten-2-one (0.161 g; 1.1 mmoles) andbis(benzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed in aSchlenk tube under an atmosphere of nitrogen. Toluene (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at70° C. with stirring for 17 hours. GC analysis showed the boronic esterof trans-4-phenyl-3-buten-2-one at 10.6 minutes (>95%) as the principalproduct.

Example 314-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-butanone

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),trans-4-phenyl-3-buten-2-one (0.161 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 18 hours. GC analysis showed a peakcorresponding to the boronic ester of trans-4-phenyl-3-buten-2-one at10.6 minutes (>95%) as the principal product.

Example 322-[(Z)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),diphenylacetylene (0.196 g; 1.1 moles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 70° C. with stirring for 88 hours. GC analysis showed the peakcorresponding to the diboronic ester of diphenylacetylene at 17.0minutes (25%), and a peak at 16.8 minutes (48%), which was shown by massspectrometry to be an isomer of the diboronic ester ofdiphenylacetylene.

Example 332-[(Z)-1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-butenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),2-methyl-1,3-pentadiene (0.120 g; 1.5 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 70° C. with stirring for 63 hours. GC analysis showed a peakcorresponding to the diboronic ester of 2-methyl-1,3-pentadiene at 10.1minutes as the principal product (12% conversion).

Example 344,4,5,5-Tetramethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclohexen-1-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1,3-cyclohexadiene (0.120 g; 1.5 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 70° C. with stirring for 63 hours. GC analysis showed two productpeaks, at 11.5 minutes (3%) and 11.7 minutes (82%). The mass spectrashow very similar fragmentation patterns, and the molecular masses areconsistent with the formation of two diboronic esters ofcyclohexa-1,3-diene.

Example 354,4,5,5-Tetramethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclohexen-1-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1,3-cyclohexadiene (0.120 g; 1.5 mmoles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 50° C. with stirring for 16 hours. GC analysis showed peaks at 11.5minutes (5%) and 11.7 minutes (84%), as in example 34, together with apeak at 14.3 minutes corresponding to the 1,4-diboronic ester of benzene(1%).

Example 364,4,5,5-Tetramethyl-2-[(Z)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butenyl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 1-phenylbutyne(0.143 g; 1.1 mmoles) and bis(dibenzylideneacetone)platinum (0.020 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. Toluene (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 70° C. with stirring for 63 hours. GCanalysis showed a peak corresponding to the diboronic ester of1-phenylbutyne at 14.2 minutes (53%), together with another peak at 13.8minutes (8%), which was shown by mass spectrometry to be an isomer ofthe diboronic ester of 1-phenylbutyne.

Example 37(Z)-1,5-Diphenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-one

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),dibenzylideneacetone (0.257 g; 1.1 mmoles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 50° C. with stirring for 15 hours. GC analysis showed a peakcorresponding to the boronic ester of dibenzylideneacetone at 18.2minutes (68%).

Example 38(Z)-1,5-Diphenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-one

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),dibenzylideneacetone (0.257 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 80° C. with stirring for 15 hours. GC analysis showed the presence ofa peak corresponding to the boronic ester of dibenzylideneacetone at18.2 minutes (30% conversion).

Example 393-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),trans-cinnamaldehyde (0.145 g; 1.1 mmoles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 50° C. with stirring for 15 hours. GC analysis showed a peakcorresponding to the boronic ester of trans-cinnamaldehyde at 10.1minutes (37%).

Example 403-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),trans-cinnamaldehyde (0.145 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 80° C. with stirring for 15 hours. GC analysis showed the presence ofa peak corresponding to the boronic ester of trans-cinnamaldehyde at10.1 minutes (12%).

Example 414,4,5,5-Tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,6-cyclooctatrien-1-yl]-1,3,2-dioxaborolane4,4,5,5-Tetramethyl-2-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,7-cyclooctatrien-1-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),1,3,5,7-cyclooctatetraene (0.114 g; 1.1 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 50° C. with stirring for 15 hours. GC analysis showed peakscorresponding to a diboronic ester of 1,3,5,7-cycloctatetraene at 14.2minutes (5% conversion) and a compound at 19.4 minutes (7% conversion)having a molecular mass corresponding to a diboronic ester of twocoupled cycloctatetraene rings.

Example 424,4,5,5-Tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-cycloocten-1-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 1,5-octadiene(0.120 g; 1.1 mmoles) and bis(dibenzylideneacetone)platinum (0.020 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. Toluene (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 50° C. with stirring for 22 hours, andthen at 80° C. with stirring for a further 17 hours. GC analysis showedtwo peaks at 13.4 minutes (52%) and 13.5 minutes (8.5%), having verysimilar fragmentation patterns, and molecular masses consistent withdiboronic esters of 1,5-octadiene.

Example 434,4,5,5-Tetramethyl-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-3-en-8-yl]-1,3,2-dioxaborolane4,4,5,5-Tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-8-en-4-yl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),dicyclopentadiene (0.145 g; 1.1 mmoles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 50° C. with stirring for 17 hours. GC analysis showed a peakcorresponding to a diboronic ester of dicyclopentadiene at 15.3 minutes(50%), together with a pair of peaks at 9.9 minutes (8%) and 10 minutes(7%), corresponding to two monohydrodeboration products.

Example 444,4,5,5-Tetramethyl-2-(4-methylcyclohexyl)-1,3,2-dioxaborolane And4,4,5,5-Tetramethyl-2-(3-methylcyclohexyl)-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),4-methyl-cyclohexene (0.110 g; 1.2 mmoles) andbis(dibenzylideneacetone)platinum (0.020 g; 0.030 mmoles) were placed ina Schlenk tube under an atmosphere of nitrogen. Toluene (5 mL, driedover 4 Å molecular sieve) was added under argon, and the tube was heatedat 80° C. with stirring for 232 hours. GC analysis showed a pair ofpeaks at 7.0 minutes (9%) and 10 minutes (5%), corresponding to twomonohydrodeboration products.

Example 454,4,5,5-Tetramethyl-2-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-7-ynyl]-1,3,2-dioxaborolane4,4,5,5-Tetramethyl-2-[(1E,7E)-2,7,8-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-octadienyl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 1,7-octadiyne(0.152 g; 1.4 mmoles) and tetrakis(triphenylphosphine)platinum (0.037 g;0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 80° C. with stirring for 14 hours. GCanalysis showed a peak at 13.2 minutes (71%) corresponding to thediboronic ester of 1,7-octadiyne, and a peak at 20.3 minutes (24%)corresponding to the tetraboronic ester of 1,7-octadiyne.

Example 464,4,5,5-Tetramethyl-2-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-7-ynyl]-1,3,2-dioxaborolane4,4,5,5-Tetramethyl-2-[(1E,7E)-2,7,8-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-octadienyl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), 1,7-octadiyne(0.055 g; 0.52 mmoles) and tetrakis(triphenylphosphine)platinum (0.037g; 0.030 mmoles) were placed in a Schlenk tube under an atmosphere ofnitrogen. DMF (5 mL, dried over 4 Å molecular sieve) was added underargon, and the tube was heated at 80° C. with stirring for 14 hours. GCanalysis showed a peak at 13.2 minutes (1%) corresponding to thediboronic ester of 1,7-octadiyne, and a peak at 20.3 minutes (87%)corresponding to the tetraboronic ester of 1,7-octadiyne.

Example 472-[(Z)-1-Butyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-3-ynyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-[(1Z,3Z)-1-Butyl-2,3,4-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-octadienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),5,7-dodecadiyne (0.250 g; 1.5 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 14 hours. GC analysis showed a peakcorresponding to unreacted starting material (25%), a peak at 15.5minutes (72%) corresponding to the diboronic ester of 5,7-dodecadiyne,and a peak at 17.4 minutes (2%) corresponding to the tetraboronic esterof 5,7-dodecadiyne.

Example 482-[(Z)-1-Butyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-3-ynyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneAnd2-[(1Z,3Z)-1-Butyl-2,3,4-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-octadienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole),5,7-dodecadiyne (0.080 g; 0.49 mmoles) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmoles) were placedin a Schlenk tube under an atmosphere of nitrogen. DMF (5 mL, dried over4 Å molecular sieve) was added under argon, and the tube was heated at80° C. with stirring for 14 hours. GC analysis showed a peak at 15.5minutes (4%) corresponding to the diboronic ester of 5,7-dodecadiyne,and a peak at 17.4 minutes (95%) corresponding to the tetraboronic esterof 5,7-dodecadiyne.

Example 494,4,5,5-Tetramethyl-2-[(E)-3-phenyl-2-propenyl]-1,3,2-dioxaborolane

The pinacol ester of diboronic acid (0.254 g; 1.0 mmole), trans-cinnamylacetate (0.176 g; 1.0 mmoles) and tris(dibenzylideneacetone)dipalladium(0.027 g; 0.030 mmoles) were placed in a Schlenk tube under anatmosphere of nitrogen. Methanol (5 mL, dried over 4 Å molecular sieve)was added under argon, and the tube was heated at 50° C. with stirringfor 63 hours. GC analysis showed a peak corresponding to the boronicester product at 10.2 minutes (60% conversion), as the sole product.

Example 502-[(Z)-2-(4H-1,3,2-Benzodioxaborinin-2-yl)-1,2-diphenylethenyl]-4H-1,3,2-benzodioxaborinine

The 2-hydroxybenzyl alcohol ester of diboronic acid (0.266 g; 1.0mmole), diphenylacetylene (0.176 g; 0.99 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 512-[(Z)-1,2-Diphenyl-2-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)ethenyl]-4,4,6-trimethyl-1,3,2-dioxaborinane

The 2-methyl-2,4-pentanediol ester of diboronic acid (0.256 g; 1.0mmole), diphenylacetylene (0.177 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.038 g; 0.031 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 522-[(Z)-2-(5,5-Diethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-diethyl-1,3,2-dioxaborinane

The 2,2-diethyl-1,3-propanediol ester of diboronic acid (0.283 g; 1.0mmole), diphenylacetylene (0.179 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 53(2-{(Z)-2-[4-(Phenoxymethyl)-1,3,2-dioxaborolan-2-yl]-1,2-diphenylethenyl}-1,3,2-dioxaborolan-4-yl)methylPhenyl Ether Or4-(Phenoxymethyl)-2-{(Z)-2-[4-(phenoxymethyl)-1,3,2-dioxaborolan-2-yl]-1,2-diphenylethenyl}-1,3,2-dioxaborolane

The 3-phenoxy-1,2-propanediol ester of diboronic acid (0.356 g; 1.0mmole), diphenylacetylene (0.180 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 54(1S,2S,6R,8S)4-{(Z)-1,2-diphenyl-2-[(1R,2R,6S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]dec-4-yl]ethenyl}-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decane

The 1R,2R,3S,5R-(−)-pinanediol ester of diboronic acid (0.359 g; 1.0mmole), diphenylacetylene (0.179 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 55(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)Tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborole

The cis-1,2-cyclopentanediol ester of diboronic acid (0.229 g; 1.0mmole), diphenylacetylene (0.181 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.039 g; 0.031 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 56(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)Tetrahydrofuro[3,4-d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydrofuro[3,4-d][1,3,2]dioxaborole

The 1,4-anhydroerythritol ester of diboronic acid (0.230 g; 1.0 mmole),diphenylacetylene (0.177 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.037 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 572-[(Z)-1,2-Diphenyl-2-(4-phenyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4-phenyl-1,3,2-dioxaborolane

The 1-phenyl-1,2-ethanediol ester of diboronic acid (0.294 g; 1.0mmole), diphenylacetylene (0.180 g; 1.0 mmole) andtetrakis(triphenylphosphine)platinum (0.038 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 58(3aR,7aS)-2-{(Z)-2-[(3aR,7aS)Hexahydro-1,3,2-benzodioxaborol-2-yl]-1,2-diphenylethenyl}hexahydro-1,3,2-benzodioxaborole

The cis-1,2-cyclohexanediol ester of diboronic acid (0.251 g; 1.0mmole), diphenylacetylene (0.176 g; 0.99 mmole) andtetrakis(triphenylphosphine)platinum (0.038 g; 0.030 mmole) were placedin a Schlenk tube open to the atmosphere. Toluene (5 mL, dried over 4 Åmolecular sieve) was added, and the sealed tube was heated at 80° C.with stirring for 72 hours. GC analysis showed the correspondingdiboronic ester of diphenylacetylene to have formed.

Example 594-[(E)-1,2-Diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]phenol

One pot synthesis of

The 1,2-bis(boronic acid pinacol ester)-1,2-diphenylethene was obtainedfollowing the method described in Example 6. After addition ofPdCl2(dppf).CH2Cl2 (27 mg), excess p-iodophenol (0.35 g) and K2CO3 (0.45g) the solution was heated for a further 21.5 h at 80° C. GC analysis ofthe solution showed only one major peak (at 19.2 mins retention time)and was shown by GC/MS to be due to the tri-aryl product.

The diboron addition to the acetylene can be carried out with the samepalladium catalyst as was used for the coupling reaction (see Example4). Then both reactions are catalysed by the same catalyst.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, and variations such as“comprises” and “comprising”, will be understood to imply the inclusionof a stated integer or step or group of integers or steps but not theexclusion of any other integer or step or group of integers or steps.

Those skilled in the art will appreciate that the invention describedherein is susceptible to variations and modifications other than thosespecifically described. It is to be understood that the inventionincludes all such variations and modifications. The invention alsoincludes all of the steps, features, compositions and compounds referredto or indicated in this specification, individually or collectively, andany and all combinations of any two or more of said steps or features.

What is claimed is:
 1. A process for preparing an organoboron compoundhaving one or more organoboron residues which comprises: (i) reacting anolefinic compound having at least one carbon to carbon double bond or anacetylenic compound having at least one carbon to carbon triple bondwith a diboron derivative in the presence of a Group 8-11 metal catalystto form an organoboron compound having an organoboronate residue on atleast one carbon atom of the respective double or triple bond; whereinsaid olefinic or acetylenic compound has at least one active hydrogencontaining substituent selected from the group consisting of hydroxy,amino, imino, carboxy, carboxylato, carboximidyl, sulfo, sulfinyl,sulfinimidyl, sulfinohydroximyl, sulfonimidyl, sulfondiimidyl,sulfonohydroximyl, sulfamyl, phosphinyl, phosphinimidyl, phosphonyl,dihydroxyphosphanyl, hydroxyphosphanyl, phosphono, phosphonato,hydrohydroxyphosphoryl, allophanyl, guanidino, hydantoyl, ureido, andureylene, and wherein said reaction of the olefinic or acetyleniccompound with the diboron derivative is an addition reaction across thedouble or triple bond respectively, or in the case of two or moreconjugated carbon to carbon double bonds, the reaction introducesorganoboronate residues on distal carbon atoms participating in theconjugation, resulting in loss of conjugation, or, in the case of anα,β-unsaturated carbonyl compound, the reaction introduces a singleorganoboronate residue on the β-carbon, resulting in loss ofα,β-unsaturation, and (ii) optionally heating the reaction mixture toresult in some hydrodeboronation.
 2. A process for covalently couplingorganic compounds which comprises: (i) reacting an olefinic compoundhaving at least one carbon to carbon double bond or an acetyleniccompound having at least one carbon to carbon triple bond with a diboronderivative in the presence of a Group 8-11 metal catalyst to form anorganoboron intermediate having an organoboronate residue on at leastone carbon atom of the respective double or triple bond; wherein saidreaction of the olefinic or acetylenic compound with the diboronderivative is an addition reaction across the double or triple bondrespectively, or, in the case of two or more conjugated carbon to carbondouble bonds, the reaction introduces organoboronate residues on distalcarbon atoms participating in the conjugation, resulting in loss ofconjugation, or, in the case of an α,β-unsaturated carbonyl compound,the reaction introduces a single organoboronate residue on the β-carbon,resulting in loss of α,β-unsaturation, (ii) adding water, water and asuitable base, or a mild oxidising agent, to decompose excess diboronderivative, and (iii) reacting the organoboron intermediate with anorganic compound having a halogen or halogen-like substituent at acoupling position in the presence of a Group 8-11 metal catalyst and asuitable base, whereby the olefinic or acetylenic compound is coupled tothe organic compound via a direct bond between the carbon atom havingthe organoboronate residue and the coupling position.
 3. A processaccording to claim 2 conducted in a single pot.
 4. A process accordingto claim 2 wherein the base added to decompose the diboron derivative isemployed to catalyse the coupling reaction.
 5. A process according toclaim 1 wherein the olefinic or acetylenic compound is selected from thegroup consisting of optionally substituted straight chain, branched orcyclic alkenes, and molecules, monomers and macromolecules which includeat least one carbon to carbon double bond; α,β-unsaturated carboncompounds; optionally substituted straight chain, branched or cyclicalkynes and molecules, monomers and macromolecules which include atleast one carbon to carbon triple bond.
 6. A process according to claim5 wherein the olefinic compound is a conjugated diene, an organiccompound having a leaving group in an allylic position, or an organiccompound having adjacent double bonds.
 7. A process according to claim 2wherein the olefinic compound is different from the organic compound. 8.A process according to claim 2 wherein the organoboron intermediate isisolated prior to reaction with the organic compound.
 9. A processaccording to claim 2 wherein the organic compound is an aromatic orpseudoaromatic ring compound having a halogen or halogen-likesubstituent at a coupling position.
 10. A process according to claim 2wherein the organic compound is an olefinic compound having a halogen orhalogen-like substituent at a vinylic coupling position.
 11. A processaccording to claim 2 wherein the organic compound is an aliphaticcompound having a halogen or halogen-like substituent at a couplingposition.
 12. A process according to claim 2 wherein the organiccompound is an acetylenic compound having a halogen or halogen-likesubstituent at a coupling position.
 13. A process according to claim 2wherein the olefinic or acetylenic compound has an active hydrogencontaining substituent.
 14. A process according to claim 6 wherein theolefinic compound has a leaving group at an allylic substitutionposition which is replaced with an organoboronate residue followingreaction with the diboron derivative.
 15. A process according to claim 1wherein the organoboron compound is hydrolyzed to produce an organicboronic acid.
 16. A process according to claim 1 wherein the reactionwith the diboron derivative is conducted in the presence of a promoter.17. A process according to claim 16 wherein the promoter is air oroxygen.
 18. A process according to claim 2 wherein the organic compoundhas more than one halogen or halogen-like substituent.
 19. A processaccording to claim 1 wherein the Group 8-11 metal catalyst comprisespalladium, nickel or platinum.
 20. A process according to claim 19wherein the Group 8-11 metal catalyst is a platinum catalyst.
 21. Aprocess according to claim 20 wherein the platinum catalyst is aplatinum complex.
 22. A process according to claim 21 wherein theplatinum complex is selected from the group consisting of Pt₃(dba)₂,Pt(PPh₃)₂Cl₂, PtCl₂, Pt(OAc)₂, PtCl₂(dppf)CH₂Cl₂, Pt(PPh₃)₄ and relatedcatalysts which are complexes of phosphine ligands, phosphite ligands,or other suitable ligands containing P and/or N atoms for co-ordinatingto the platinum atoms.
 23. A process according to claim 21 wherein theplatinum complex is tethered on a solid support.
 24. A process accordingto claim 20 wherein the platinum catalyst is selected from platinumblack, platinum on carbon and platinum clusters or a platinum complex ora platinum complex tethered on a solid support.
 25. A process accordingto claim 19 wherein the Group 8-11 metal catalyst is a palladiumcatalyst.
 26. A process according to claim 23 wherein the catalyst isselected from the group consisting of palladium black, palladium oncarbon, palladium clusters and palladium in porous glass.
 27. A processaccording to claim 19 wherein the catalyst is a nickel complex.
 28. Aprocess according to claim 27 wherein the catalyst is selected from thegroup consisting of nickel black, Raney nickel, nickel on carbon andnickel clusters or a nickel complex or a nickel complex tethered on asolid support.
 29. A process according to claim 1 wherein the diboronderivative is an ester or other stable derivative of diboronic acid. 30.A process of claim 1 conducted in the presence of a protic solvent. 31.A process of claim 2 wherein the suitable base is selected from thegroup consisting of aryl and alkyl carboxylates, carbonates, fluoridesand phosphates of Li, Na, K, Rb, Cs, ammonium and alkylammonium.
 32. Aprocess of claim 2 wherein the suitable base is selected from the groupconsisting of aryl and alkyl carboxylates, fluorides, hydroxides andcarbonates of Li, Na, K, Rb, Cs, ammonium, alkylammonium, Mg, Ca and Ba;phosphates, and arylphosphates of Li, Na, K, Rb and Cs; phosphate estersof Li, Na, K, Rb and Cs, phenoxides of Li, Na, K, Rb and Cs; alkoxidesof Li, Na, K, Rb and Cs; and thallium hydroxide.
 33. A process of claim2 wherein the suitable base is selected from cesium carbonate, potassiumcarbonate, potassium phosphate and alkali metal hydroxides.
 34. Aprocess of claim 2 wherein one of said olefinic compound and saidorganic compound is a polymer.
 35. A process of claim 2 wherein eitherthe olefinic compound or the organic compound is chemically linked to asolid polymer support.
 36. A process according to claim 1 wherein theformed organoboron compound has an organoboronate residue on each carbonatom of the respective double or triple bond.
 37. A process according toclaim 36 wherein the reaction mixture is heated in the presence of abase such that some or all of the organic intermediate undergoesmonohydroboronation.
 38. A process according to claim 2 wherein thediboron derivative is chiral having an enantiomeric excess of one formrelative to another such that the formed organoboron intermediate ischiral having an enantiomeric excess.
 39. A process according to claim 1wherein the diboron derivative is chiral having an enantiomeric excessof one form relative to another such that the formed organoboroncompound is chiral having an enantiomeric excess of one form relative toanother.
 40. Organoboron compounds selected from the group consistingof:2-[(Z)-2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-dimethyl-1,3,2-dioxaborinane,2-[(Z)-2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1-ethyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane,2-[(Z)-2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1-phenyl-1-butenyl]-5,5-dimethyl-1,3,2-dioxaborinane,methyl(Z)-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-nonenoate,(E)4-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one,(Z)-4-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-2-one,2-[(E)-1-(1-cyclohexen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,1-[(E)-1,2-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]cyclohexanol,(E)-N,N-dimethyl-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amine,(E)-3-ethyl-1,2-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-amine,(E)-N,N-di(2-propynyl)-2,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-amine,4,4-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexanone,4,4,5,5-tetramethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclohexen-1yl]-1,3,2-dioxaborolane,(Z)-1,5-diphenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-penten-3-one,3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal,4,4,5,5-tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,6-cyclooctatrien-1-yl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4,7-cyclooctatrien-1-yl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-cycloocten-1-yl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-3-en-8-yl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)tricyclo[5.2.1.02,6]dec-8-en-4-yl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-(4-methylcyclohexyl)-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-(3-methylcyclohexyl)-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-7-ynyl]-1,3,2-dioxaborolane,4,4,5,5-tetramethyl-2-[(1E,7E)-2,7,8-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-octadienyl]-1,3,2-dioxaborolane,2-[(Z)-1-butyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-octen-3-ynyl]4,4,5,5-tetramethyl-1,3,2-dioxaborolane,2-[(1Z,3Z)-1-butyl-2,3,4-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-octadienyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,2-[(Z)-2-(4H-1,3,2-benzodioxaborinin-2-yl)-1,2-diphenylethenyl]-4H-1,3,2-benzodioxaborinine,2-[(Z)-1,2-diphenyl-2-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)ethenyl]-4,4,6-trimethyl-1,3,2-dioxaborinane,2-[(Z)-2-(5,5-diethyl-1,3,2-dioxaborinan-2-yl)-1,2-diphenylethenyl]-5,5-diethyl-1,3,2-dioxaborinane,(2-{(Z)-2-[4-(phenoxymethyl)-1,3,2-dioxaborolan-2-yl]-1,2-diphenylethenyl}-1,3,2-dioxaborolan-4-yl)methylphenyl ether,(1S,2S,6R,8S)-4-{(Z)-1,2-diphenyl-2-[(1R,2R,6S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]dec-4-yl]ethenyl}-2,9,9-trimethyl-3,5-dioxa4-boratricyclo[6.1.1.02,6]decane,(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydro-3aH-cyclopenta[d][1,3,2]dioxaborole,(3aR,6aS)-2-{(Z)-2-[(3aR,6aS)tetrahydrofuro[3,4-d][1,3,2]dioxaborol-2-yl]-1,2-diphenylethenyl}tetrahydrofuro[3,4-d][1,3,2]dioxaborole,2-[(Z)-1,2-diphenyl-2-(4-phenyl-1,3,2-dioxaborolan-2-yl)ethenyl]-4-phenyl-1,3,2-dioxaborolane,and(3aR,7aS)-2-{(Z)-2-[(3aR,7aS)hexahydro-1,3,2-bexzodioxaborol-2-yl]-1,2-diphenylethenyl}hexahydro-1,3,2-benzodioxaborole.41. A process according to claim 38 wherein the chirality of organoboronintermediate results in a coupled product having a chirality and anenantiomeric excess of one enantiomer relative to another.